We propose to investigate and develop novel dental materials that are antibacterial and/or fluoride-releasing and act synergistically to form a highly effective caries-inhibition restorative system. Such materials are expected to have an enormous impact on the oral health of the most vulnerable, high caries-risk, portion of the population: the medically-compromised who suffer from xerostomia or dry mouth (due to Sjvgren's syndrome, diabetes, head and neck irradiation, and medications), children, the elderly, and low socio-economic groups. Dental caries continues to be a worldwide pandemic disease. While resin-based dental composites (RBC) are widely used to restore carious teeth, secondary (recurrent) caries remains the leading cause cited for their replacement. Thus, much effort has been directed towards development of composites that release caries-preventing agents such as fluoride. Nevertheless, current dental composites are deficient in both fluoride-release and fluoride-recharge capabilities, and very few have antimicrobial or other capabilities for preventing plaque. Furthermore, all dental composites and compomers require bonding agents in order to reduce marginal leakage and limit secondary caries. Yet, both non-fluoride-releasing and low-fluoride-releasing bonding agents are inherently barriers to the transport of fluoride to caries-prone areas. Another problem is that the majority of self-etching dental bonding agents are susceptible to hydrolytical degradation, which leads to eventual leakage, secondary caries and reduced RBC lifetime. On the primary caries prevention front, sealants, including fluoride-releasing sealants, have shown caries-prevention efficacy, yet the dental profession has been slow to adopt sealants due, in part, to the fear that caries will continue to progress under sealed pits and fissures. The goal of this project is to develop novel monomers with enhanced antibacterial activity, enhanced fluoride release and recharge, and other capabilities, and combine them with fluoride-releasing fillers and bioactive fillers to overcome the multiple problems associated with current composites, adhesives and sealants that limit their caries-inhibition efficacy and restoration longevity. This project has four specific aims: (1) to formulate and optimize a novel antibacterial fluoride releasing dental composite, (2) to formulate and optimize a novel hydrolytically stable fluoride-releasing dental bonding agent, (3) to formulate and characterize a novel antibacterial bioactive sealant that releases calcium, phosphate, and fluoride, (4) to test the overall caries-inhibition efficacy of the novel anticariogenic dental material system by artificial caries models. The hypotheses are: (1) Dental materials containing the new fluoride exchange monomers will have enhanced fluoride release and recharge capabilities while maintaining adequate or improved physical and mechanical properties. (2) The combination of antimicrobial activity with enhanced remineralization capability will synergistically lead to significantly higher caries-inhibiting efficacy of the restorative materials. (3) The combined use of an antibacterial fluoride-releasing composite, bonding agent and bioactive sealant will further reduce caries. This project seeks to develop a series of antibacterial, fluoride-releasing, and bioactive dental materials. These materials are expected to have enhanced anti-caries efficacy over existing resin-based dental materials. The development of these materials has the potential to make a huge impact on oral health care and oral health quality-of-life, in particular for the vast number of high-caries-risk patients (medically compromised who suffer from xerostomia or dry mouth, children, elderly, mentally or physically challenged).